Corporate Overview. March 2018

Corporate Overview March 2018

Forward looking statements This presentation contains forward looking statements, including, but not limited to, statements related to financial results and trends; the process and timing of anticipated future development of AcelRx's product candidates, DSUVIA (sufentanil sublingual tablet, 30 mcg), known as DZUVEO (formerly ARX 04) outside the United States, and ZALVISO (the sufentanil sublingual tablet system), including the timing and review of the NDA resubmission for DSUVIA based on the outcome of the Type A FDA meeting; the timing of the MAA opinion on DZUVEO, the anticipated timing of any FDA advisory committee meeting or PDUFA date regarding DSUVIA following the DSUVIA NDA resubmission; the DZUVEO and DSUVIA clinical trial results; AcelRx's pathway forward towards gaining approval of ZALVISO in the United States; the timing and anticipated resubmission of the ZALVISO NDA to the FDA, including the scope and timing of the resubmission and the FDA review time; the status of the collaboration and license agreement with Grünenthal or any other future potential collaborations, including potential milestones and royalty payments under the Grünenthal agreement; and the therapeutic and commercial potential of AcelRx's product candidates, including potential market opportunities for DSUVIA, DZUVEO and ZALVISO; and projected cash flows. These forward looking statements are based on AcelRx s current expectations and inherently involve significant risks and uncertainties. AcelRx s actual results and timing of events could differ materially from those anticipated in such forward looking statements and as a result of these risks and uncertainties, which include, without limitation risks related to AcelRx s DSUVIA and DZUVEO development programs, including EMA review of the DZUVEO MAA, and the possibility that EMA may dispute or interpret differently clinical results obtained from the DZUVEO Phase 2 and 3 studies; the possibility that the FDA may dispute or interpret differently the results of the Company s planned Human Factors study to validate the revised Directions For Use or the supplemental information included in the planned resubmission of the NDA for DSUVIA; the possibility that the FDA may dispute or interpret differently the results from the ZALVISO development program, including the results from the IAP312 clinical trial; the resubmission of the ZALVISO NDA to the FDA; any delays or inability to obtain and maintain regulatory approval of its product candidates, including DSUVIA in the United States, DZUVEO in Europe and ZALVISO in the United States; the uncertain clinical development process, including adverse events; the success, cost and timing of all development activities and clinical trials; the accuracy of AcelRx's estimates regarding expenses, capital requirements and the need for financing; and other risks detailed in the Risk Factors and elsewhere in AcelRx's US Securities and Exchange Commission filings and reports, including its Annual Report on Form 10 K filed with the SEC on March 8, 2018. AcelRx undertakes no duty or obligation to update any forward looking statements contained in this presentation as a result of new information, future events or changes in its expectations. 2

Key leadership Vincent Angotti Chief Executive Officer Appointed Chief Executive Officer and a member of the Company's Board of Directors in March 2017 Over 25 years of experience leading executive and commercial teams at public and private life sciences companies Previous positions: CEO of XenoPort, Inc., SVP Sales & Marketing of Reliant Pharmaceuticals, Inc., Career began at Novartis Pharmaceuticals where he held various roles of increasing responsibility Raffi Asadorian Chief Financial Officer Appointed Chief Financial Officer effective August 2017 Over two decades of finance, strategy and corporate development experience at publicly traded and private equity owned companies Previous positions: CFO of Amyris, Unilabs, and PLIVA. Career began at PricewaterhouseCoopers where he was a Partner in its Transaction Services group Pamela P. Palmer, MD, PhD Chief Medical Officer Co founded AcelRx in July 2005 and serves as Director and Chief Medical Officer Director of the UCSF Pain Center for Advanced Research and Education (PainCARE) from 2005 to 2009; Co founded Omeros Corporation in 1994 Dr. Palmer has a medical degree and a doctorate in neuroscience from Stanford University, and continued on to the University of California, San Francisco for her anesthesia residency 3

Clarifying pain management Acute Chronic Medically Supervised Patient Retail Script 4

Clarifying the opioid crisis 0.7% Of sustained opioid use originates from an inpatient experience (1) Patients with sustained opioid use 0.70% Inpatient experience No inpatient experience OUR FOCUS Treatment for moderate-to-severe acute pain within a medically supervised environment 5 1. Schoenfeld et al. JAMA Surg 152 (12), 1175-1176. 2017 Dec 01

Late stage pipeline of sufentanil sublingual products for moderate to severe acute pain Single dose sufentanil sublingual 30 mcg tablet in a pre filled applicator HCP administered in a Medically Supervised Setting US/EU large potential market opportunity in multiple settings 1 Multiple doses sufentanil sublingual 15 mcg tablets in a 40 count cartridge Patient administered in a Medically Supervised Setting Approved and Marketed in EU US: potentially complementary market opportunity with DSUVIA 6 1. Data on file. In-house commissioned market research. QuintilesIMS, ARX-04 and ZALVISO US forecast December 2016 & ARX-04: Asset forecast for Europe Emergency medical services and Postoperative pain May 2016

Current IV opioids on the market do not fully address the patient or healthcare professional needs Slower acting opioids (IV morphine) Fast acting, but fast offset opioids (IV fentanyl/sufentanil) 3 hrs blood:brain equilibration 6 min blood:brain equilibration 7 PD: Lötsch. J Pain Symptom Manage. 2005;29:S90

Sufentanil sublingual addresses an unmet need in acute pain management Sufentanil Sublingual (30 mcg) Clinical trials show analgesia as early as 15 minutes and with a duration of ~3 hours 8 SAP 301, SAP 302 (data on file)

Proprietary sufentanil sublingual tablets have unique properties Small size dissolves in minutes Sublingual absorption potentially maintains therapeutic levels for 3 hours Minimizes saliva production to limit swallowed drug and maintain sublingual bioavailability Bioadhesive to keep in place under tongue Discrete dosing unit may reduce dosing errors and mitigate risk of diversion with clear liquids 9

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DSUVIA designed in collaboration with the Department of Defense Light Weight, Extreme Environment Tested, Easily Handled with Gloves 1 Clear plastic to allow tablet visibility Pre filled tablet Non retractable pusher Removable lock to avoid premature actuation (not shown) 11 1. AcelRx data on file (2015-2016) MRC-0152 MRC-015208MAR18 08MAR18

DSUVIA has an opportunity to address unmet needs for patients and hospitals Patient experience Ease of use Hospital/ER efficiency No risk of IV infection Lower total cost 12

NDA and MAA submitted for the treatment of moderateto severe acute pain in medically supervised settings 13 CRL received October 2017 FDA Type A meeting end of January 2018 and expected NDA resubmission in early Q2 2018 Label: Medically Supervised Settings Administered by Healthcare Professional No retail distribution REMS program CHMP opinion expected first half of 2018

DSUVIA NDA resubmission expected in Q2 2018 12 doses/day Reduced from 24/day Substantial Safety Data Available Patient data supports lowered max daily dose Human Factors Study Validate revised Directions For Use Favorable Type A meeting outcome leading to an expected NDA resubmission in Q2 2018 following completion of HF study In light of the lowered maximum DSUVIA dose, the FDA indicated it was expected that the existing DSUVIA and Zalviso data may be sufficient HF study expected to be completed by next month 14

904 total patients in DSUVIA database across a variety of surgery / injury types SAP202: Post operative musculoskeletal 904 Total patients originally submitted with NDA SAP301: Post operative soft tissue SAP302: ER setting, multiple injury types SAP303: Post operative older population, comorbidities Select Zalviso patients Pivotal trials demonstrated statistically significant pain reduction compared to placebo (SAP202, p=0.005; SAP301, p<0.001) Combined clinical studies showed no meaningful differences in Adverse Events compared to placebo 15 Most common AE s were nausea, hypotension, vomiting

In emergency settings, DSUVIA showed clinically meaningful pain reduction with a single dose Mean Pain Intensity (SAP302) 8.08 NRS Score 6.99 6.23 5.51 5.2 Baseline pain intensity was 8.1/10 35.7% Reduction in Pain Intensity by 60 Minutes Literature supports a pain intensity reduction of 1.3 as clinically meaningful to the patient 1 0 15 30 45 60 Time (Minutes) 16 1.Bijur, Polly E., et al. Validation of a Verbally Administered Numerical Rating Scale of Acute Pain four Use in the Emergency Department. Academy Emergency Medicine. 2003;10: 390-392.

91.9M adult moderate to severe acute pain patient visits in medically supervised settings Emergency department Inpatient/other surgery Outpatient surgery Other procedures 18.7 11 91.9M 51.5 10.7 17 Source: Aggregated Medical Literature review, QuintilesIMS primary market research, QuintilesIMS analysis 2016. ARX-04 and Zalviso US data-december 2016 MRC-0152 MRC-0152 08MAR18 08MAR18

Initial emergency department target of 18M adult patient visits annually receiving IVs exclusively for pain meds 112M Initial Emergency Department Target patient visits 51M patients visits 33M patients visits 18M Total ER patient visits Moderate tosevere acute pain in ER Opioid for pain in ER IV for pain only in ER 18 Source: Aggregated Medical Literature review, QuintilesIMS primary market research, Qunitles IMS analysis 2016

The number of emergency departments is declining while annual visits are on the rise Emergency Departments ED Visits (Millions) NUMBER OF EMERGENCY DEPARTMENTS 5100 5000 4900 4800 4700 4600 4500 4400 4300 4200 160 140 120 100 80 60 40 20 ED VISITS (MILLIONS) 4100 94 95 96 97 98 99 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 YEAR 0 19 1. Aha.org [Internet] Trend Watch Chartbook 2015; c2015. Available from http://www.aha.org/research/reports/tw/chartbook/2015/15chartbook.pdf (Graph) (accessed 2016, November 23)

IV administration is resource and cost intensive Efficiency Costs of Initiating IV 1,2 Lack of bed space, HCP availability decreases patient flow Component Costs of IV Dose 3 $7 $4 $5 $15 Failure rates of IV access reported as high as 12 26% $62 > $140 $15 Difficult IV access may require advanced techniques, such as ultrasound guidance, increasing time to IV placement by 118 135 minutes Drug Lidocaine Saline Bag $37 Catheter Tubing IV Pump 19 1. Sabri, A et al. Biomed Mater Eng 2013; 23(1-2):93-108 2. Witting MD et al J Emer Med 2017; 53(2):172-177 3. Palmer PP et al. J Health Econ Outcomes Res 2017; 5(1) 1-15

DSUVIA outpatient surgery opportunity is estimated at 11M adult patient visits annually 27M Outpatient surgery target patients visits 11M patients visits 21 Outpatient procedures Source: Aggregated Medical Literature review, QuintilesIMS primary market research, Qunitles IMS analysis 2016 Moderate to severe acute pain patients

Outpatient surgery recovery is time sensitive to ensure patient throughput Optimal analgesic profile Phase 1: 30 minutes Stabilize patient after surgery Onset of action as early as 15 minutes Phase 2: 60 90 minutes Pain management and side effect monitoring Duration lasts through discharge Discharge Script for oral pain medications 22 1. QuintilesIMS, ARX-04 and Zalviso US data - December 2016

A clear unmet need in acute pain management IV Fentanyl Fast onset IV Hydromorphone? Invasive Non-invasive Percocet IV Morphine Slow onset Vicodin 23 Source: Competitive landscape review-see full report for details (indicative only), Greater Than One primary market research, Greater Than One analysis 2017

DSUVIA may address unmet clinical need and hospital efficiency Clinical Hospital Efficiency 24

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Zalviso : Sufentanil Sublingual 15 mcg in a Patient Controlled Analgesia (PCA) System Proposed Indication Management of moderate to severe acute pain in adult patients in an in patient hospital setting Dosing 40 count 15 mcg tablets / cartridge Development Status Clinical Study in life portion completed NDA resubmission planned for H218 Type II resubmission 6 month review Launched in Europe April 2016 by our partner 26 MRC-0152 MRC-015208MAR18 08MAR18

Why PCA for inpatient (>24hrs) post operative pain? PCA has been shown to be more effective in treating inpatient post operative pain than intermittent IM or IV injections 1 Increased control over pain relief Provide higher patient satisfaction Lower pre operative anxiety and post operative depressive symptoms Other advantages include not having to receive injections, not having to wait for pain relief, and not having to summon nurses. Intravenous PCA Zalviso PCA 27 1. Patak L et al. Reg Anseth Pain Med. 2013 Jul-Aug 38(4);326-333

Zalviso IAP312 trial results achieved study objectives 2.2% 7 patients out of 320 experienced a device error (2.2%) 4 of 7 pts. experienced analgesic gap due to tablet not dispensed Standard of care (IV PCA) device error ~ 12% 1 <0.1% 7 tablets discovered by HCP out of 7,293 dispensed (<0.1%) The 7 misplaced tablets occurred with 6 patients No repeat dropped tablets following re training Patient Global Assessment % Success PGA 24 hrs 86 PGA 48 hrs 89 PGA 72 hrs 100 HCP Global Assessment % Success HPGA 24 hrs 91 HPGA 48 hrs 95 HPGA 72 hrs 100 28 1. Panchal, Anesth Analg. 2007 Nov;105(5):1437-41

Zalviso inpatient acute pain opportunity in the US is estimated at ~10M adult patient visits annually 105M Initial Inpatient Target patient visits 31M patient visits Total hospital patient visits Moderate to severe acute pain patients ~10M Inpatient > 24 hours 29 Source: QuintilesIMS, ARX-04 and Zalviso US data - December 2016

Zalviso is being commercialized in Europe with our partner, Grünenthal 30 Source: Zalviso EU website, http://zalviso.eu/, accessed Sept 7, 2017

Grunenthal s EU Zalviso launch progressing well with a total use by over 17,800 patients through Jan 2018 # of Patients 6090 3679 466 2078 907 1899 * including Phase IIIb 1182 157 1105* 186 1800 1600 1400 1200 1000 800 600 400 200 0 Patients December decline in number of patients attributed to Christmas holidays; continues to progress well in 2018 Apr 16 Mai 16 Jun 16 Jul 16 Aug 16 Sep 16 Oct 16 Nov 16 Dez 16 Jan 17 Feb 17 Mrz 17 Apr 17 Mai 17 Jun 17 Jul 17 Aug 17 Sep 17 Oct 17 Nov 17 Dez 17 Jan 18 Patienten # of Hospitals 931 22 32 10 300 250 200 Hospitals (cum.) 48 10 21 4 14 12 150 100 50 0 Apr 16 Mai 16 Jun 16 Jul 16 Aug 16 Sep 16 Oct 16 Nov 16 Dez 16 Jan 17 Feb 17 Mrz 17 Apr 17 Mai 17 Jun 17 Jul 17 Aug 17 Sep 17 Oct 17 Nov 17 Dez 17 Jan 18 28 Hospitäler (cum.)

Near term upcoming milestones Q1 2018 Q2 2018 Q3 2018 Q4 2018 Type A meeting Q2 Expect completed HF study Plan to resubmit DSUVIA NDA CHMP opinion on DZUVEO anticipated Q3 Expected Advisory Committee meeting Potential MAA approval for DZUVEO H2 Q4 Expected DSUVIA PDUFA date Expected Zalviso NDA resubmission 32

AcelRx investment highlights DSUVIA NDA expected to be resubmitted in Q2 2018 Expect to refile after completing HF study to validate DFU CHMP opinion H1 2018 (DZUVEO) US market opportunity is over 91M patients in multiple settings 1 ZALVISO resubmission planned in H2 2018 Successfully completed IAP312 study Commercial launch in Europe over 16,000 patients in over 200 hospitals through end of 2017 43 issued patents; 42 pending $60.5 million cash as of December 31, 2017 $10 11 million quarterly cash burn pre commercial 33 1. Data on file. In-house commissioned market research. QuintilesIMS, ARX-04 and ZALVISO US forecast December 2016

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